Inclusion of CD80 in HSV targets the recombinant virus to PD-L1 on DCs and allows productive infection and robust immune responses

• Published in: PloS one 2014-01, Vol.9 (1), p.e87617-e87617
• Main Authors: Mott, Kevin R, Allen, Sariah J, Zandian, Mandana, Akbari, Omid, Hamrah, Pedram, Maazi, Hadi, Wechsler, Steven L, Sharpe, Arlene H, Freeman, Gordon J, Ghiasi, Homayon
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - genetics; Adjuvants, Immunologic - metabolism; Animals; Antigens; B cells; B7-1 Antigen - genetics; B7-1 Antigen - metabolism; B7-H1 Antigen - metabolism; Biology; Blotting, Southern; Bone marrow; CD80 antigen; Cell activation; Cell growth; Cytokines; Dendritic cells; Dendritic Cells - metabolism; DNA Primers - genetics; Flow Cytometry; Fluorescent Antibody Technique; Genes; Genetic Engineering; Genomes; Health aspects; Herpes Simplex - genetics; Herpes Simplex - immunology; Herpes viruses; Herpesvirus 1, Human - genetics; Immune response; Immune system; Immunology; Infection; Infections; Kinetics; Latency; Ligands; Lymphocytes; Lymphocytes T; Medicine; MicroRNAs - genetics; Neurobiology; Neurosciences; PD-L1 protein; Rabbits; Real-Time Polymerase Chain Reaction; Recombination, Genetic - genetics; Skin; Surgery; T cells; Transcription; Vaccine efficacy; Vaccines; Viral Vaccines - genetics; Virus replication; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0087617

CD80 plays a critical role in stimulation of T cells and subsequent control of infection. To investigate the effect of CD80 on HSV-1 infection, we constructed a recombinant HSV-1 virus that expresses two copies of the CD80 gene in place of the latency associated transcript (LAT). This mutant virus (HSV-CD80) expressed high levels of CD80 and had similar virus replication kinetics as control viruses in rabbit skin cells. In contrast to parental virus, this CD80 expressing recombinant virus replicated efficiently in immature dendritic cells (DCs). Additionally, the susceptibility of immature DCs to HSV-CD80 infection was mediated by CD80 binding to PD-L1 on DCs. This interaction also contributed to a significant increase in T cell activation. Taken together, these results suggest that inclusion of CD80 as a vaccine adjuvant may promote increased vaccine efficacy by enhancing the immune response directly and also indirectly by targeting to DC.